Research progress of Hofmann rearrangement reaction

doi:10.11949/0438-1157.20200890

Abstract

Abstract:

Hoffman rearrangement reaction is an important method for preparing primary amines and their derivatives, and has a wide range of applications in the fields of drug synthesis and functional material preparation. At present, the traditional Hofmann rearrangement processes involved liquid bromine and batch reactors encounter lots of problems in large-scale production, such as low reaction efficiency, complex operation and poor safety. To solve these problems, scientific and engineering researchers have made a lot of efforts, and a large number of studies about optimization of reaction conditions and process intensification have been reported. Through the optimization of reaction conditions, many mild and highly selective reaction reagents have been developed, which provide more choices for the reaction scheme design of different amide substrates. The emergence of novel reaction process intensification technologies such as microwave assistance, electrochemistry and micro-reactors has created favorable conditions for the realization of high-efficiency and environmentally friendly Hofmann rearrangement reaction. This review focuses on the latest research progress of Hofmann rearrangement reaction in the optimization of reaction conditions and process intensification. On this basis, the future research direction of this reaction was prospected.

Key words: Hofmann rearrangement, oxidation, amide, micro-chemical, microwave, electrochemistry, micro-reactor

摘要：

霍夫曼重排反应作为制备伯胺及其衍生物的一种重要手段，在药物合成和功能材料制备等领域有广泛的应用。传统霍夫曼重排反应工艺存在反应效率低、流程烦琐和安全性差等问题。针对以上问题，研究者们主要从反应条件优化和过程强化两方面入手。通过反应条件优化，发展了许多温和、高选择性的反应工艺条件，为不同酰胺底物的反应方案设计提供了更多选择；微波辅助、电化学合成以及微化工技术等新型反应过程强化技术的出现，为实现高效绿色的霍夫曼重排反应创造了有利的条件。本文重点阐述了霍夫曼重排反应在反应条件优化和过程强化方面的最新研究进展。在此基础上，对该反应未来的研究方向进行了展望。

关键词: 霍夫曼重排, 氧化, 酰胺, 微化工, 微波, 电化学, 微反应器

CLC Number:

TQ 463

HUANG Jinpei, HUANG Dan, WANG Fajun, XU Jianhong. Research progress of Hofmann rearrangement reaction[J]. CIESC Journal, 2021, 72(1): 158-166.

黄晋培, 黄丹, 王法军, 徐建鸿. 霍夫曼重排反应过程的研究进展[J]. 化工学报, 2021, 72(1): 158-166.

Figures/Tables 10

Fig.1 Hofmann rearrangement reaction process

Fig.2 General mechanistic aspect of Hofmann rearrangement

Fig.3 Hofmann rearrangement with different oxidants

Fig.4 Hofmann rearrangement with different bases

Fig.5 Catalytic version of Hofmann rearrangement

Fig.6 Hofmann rearrangement with ionic liquid

Fig.7 Hofmann rearrangement with microwave assistance

Fig.8 Electrochemical Hofmann rearrangement

Fig.9 Hofmann rearrangement using microreactor platform

Fig.10 Continuous synthesis of Gabapentin with a microreaction system

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